Background: To investigate the prognostic value of PD-1 and PD-L1 expression in patients with high-grade upper tract urothelial carcinoma (UTUC). Methods: Tissue microarrays were created using 448 patients from the International UTUC collaboration who underwent extirpative surgery for high-grade UTUC and stained for PD-1 (antibody (AB): NAT105, diluted 1:250 from Ventana) and PD-L1 (AB: E1L3N prediluted from Cell Signaling). PD-1 and PD-L1 expression was assessed in a semi-quantitative fashion and any percentage of staining of the tumor cells (PD-L1) and tumor-infiltrating lymphocytes (PD-1) was considered positive. Univariate (UVA) and multivariate analyses (MVA) were performed to assess independent prognosticators of oncological outcomes. No funding was received. Results: Median age of the cohort was 69.2 years and 56.5% of patients were male. PD-L1 and PD-1 were positive in 24.1% and 37.5% of patients. PD-L1 positivity was associated with favorable pathological stage, where as PD-1 positivity was significantly associated with pelvicalyceal location, lymph node metastases, non-organ confined disease, presence of lymphovascular invasion, sessile architecture, necrosis, concomitant CIS, and history of non-muscle invasive bladder cancer. PD-L1 positivity was not significantly associated with survival outcomes. In Cox regression UVA, PD-1 positivity was associated with worse recurrence-free survival (RFS) (HR 1.5 (95%CI 1.08-2.14, p=0.016)), cancer-specific survival (CSS) (HR 1.5 (95%CI 1.07-2.19, p=0.021)), and overall survival (OS) (HR 1.5 (95%CI 1.10-1.97, p=0.009)). However in MVA, PD-1 positivity was not found to be an independent predictor of RFS, CSS or OS. Conclusions: PD-1 positivity of tumor-infiltrating lymphocytes was associated with adverse pathological criteria and was a significant prognosticator for RFS, CSS and OS on UVA in patients treated with extirpative surgery for high-grade UTUC in a large, multi-institutional cohort. In MVA, the independent prognostic value of PD-1 was not confirmed. PD-L1 positivity was associated with lower tumor stage, but not with other pathological characteristics or survival outcomes.